We plan to study the effect of prostaglandin synthetase inhibitors on vascular resistance of renal and cutaneous vascular beds in the dog and on the renal vasodilator effect of P-113. Arterial and venous PGE2 concentration will be measured by radioimmunoassay and correlation sought for inhibition of prostaglandin synthesis and release and resistance changes caused by the inhibitors. Studies will also be carried out in conscious dogs in which blood pressure and renal blood flow are monitored to ascertain what changes in renal vascular resitance, renin, and PGE2 levels occur during establishment of renal hypertension. The nature of the neurotransmitter mediating sustained sympathetic vasodilatation in dog's paw will be sought. The possibility that sympathetic stimulation after adrenergic blockade may induce synthesis and release of a PGE which mediates the response will be examined.